The design of this project is based on my observations that (a) embryonic spinal cord cells produce plasminogen activator and (b) the proteolytic plasmin-generating system is involved in the regulation of the developmental process of embryonic spinal cord in culture specifically, in the migration and wrapping of neuronal extensions by glial cells. The plasmin-generating system is considered as a possible general enzymatic mechanism for tissue remodeling processes. This system is found in the serum and is composed of the pa plasminogena and plasminogen activator. The objectives of the project are to determine the precise regulatory role of (a) plasmin and/or plasminogen activator, and (b) neuronal-glial cellular communication, in tissue remodelling which occur in developing nervous system (spinal cord) in vivo and in culture. The objectives will be met by a stepwise study which will determine: A. The role of plasmin activity in modulating the spatial organization of embryonic spinal cord cells. B. The production of plasminogen activator as a function of differentiation in culture and in vivo. C. The possible regulatory role of protease inhibitors in morphogenesis. D. The cell type(s) which produce (s) the plasminogen activator. E. The production of plasminogen activator as a function of neuronal-glial interactions and of certain serum components (several hormones). The scientific methods to be employed in this study combine a wide range of approaches and techniques, biochemical (enzymatic), cellular (cell culture), and ultrastructural. This project will provide fundamental information about the regulatory mechanisms, both serum and cellularly mediated, which are involved in the control of differentiating nervous tissue.